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Test Code D15F 15q11.2 Duplication, FISH

Useful For

Evaluating patients with autistic spectrum disorders for 15q11.1-11.3 region

 

Confirming the origin of supernumerary marker chromosomes suspected of being derived from chromosome 15

 

Resolving the origin when duplication of 15q11.1-11.3 is identified via molecular multiplex ligation-dependent probe amplification analysis

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
_PBCT Probe, +2 No, (Bill Only) No
_PADD Probe, +1 No, (Bill Only) No
_PB02 Probe, +2 No, (Bill Only) No
_PB03 Probe, +3 No, (Bill Only) No
_ML10 Metaphases, 1-9 No, (Bill Only) No
_M30 Metaphases, >=10 No, (Bill Only) No
_IL25 Interphases, <25 No, (Bill Only) No
_I099 Interphases, 25-99 No, (Bill Only) No
_I300 Interphases, >=100 No, (Bill Only) No

Testing Algorithm

This test includes a charge for application of the first probe set (2 FISH probes) and professional interpretation of results. Additional charges will be incurred for application of all reflex probes performed. Analysis charges will be incurred based on the number of cells analyzed per probe set. If no cells are available for analysis, no analysis charges will be incurred.

Method Name

Fluorescence In Situ Hybridization (FISH)

Reporting Name

15q11.2 Duplication, FISH

Specimen Type

Varies


Specimen Required


Provide a reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.

 

Advise Express Mail or equivalent if not on courier service.

 

Submit only 1 of the following specimens:

 

Preferred:

Specimen Type: Blood

Container/Tube: Green top (sodium heparin)

Specimen Volume: 5 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Other anticoagulants are not recommended and are harmful to the viability of the cells.

 

Acceptable:

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20-25 mL

Collection Instructions:

1. Optimal timing for specimen collection is during 14 to 18 weeks of gestation, but specimens collected at other weeks of gestation are also accepted. Provide gestational age at the time of amniocentesis.

2. Discard the first 2 mL of amniotic fluid.

Additional Information:

1. Place the tubes in a Styrofoam container (T329).

2. Fill remaining space with packing material.

3. Unavoidably, about 1% to 2% of mailed-in specimens are not viable.

4. Bloody specimens are undesirable.

5. If the specimen does not grow in culture, you will be notified within 7 days of receipt.

6. Results will be reported and also telephoned or faxed, if requested.

 

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20-25 mg

Collection Instructions:

1. Collect specimen by the transabdominal or transcervical method.

2. Transfer chorionic villi to a Petri dish containing transport medium (T095).

3. Using a stereomicroscope and sterile forceps, assess the quality and quantity of the villi and remove any blood clots and maternal decidua.

 

Specimen Type: Skin biopsy

Container/Tube: Sterile container with sterile Hank's balanced salt solution (T132), Ringer's solution, or normal saline

Specimen Volume: 4 mm diameter

Collection Instructions:

1. Wash biopsy site with an antiseptic soap.

2. Thoroughly rinse area with sterile water.

3. Do not use alcohol or iodine preparations.

4. A local anesthetic may be used.

5. Biopsy specimens are best taken by punch biopsy to include full thickness of dermis.


Specimen Stability Information

Specimen Type Temperature Time
Varies Refrigerated (preferred)
  Ambient 

Reject Due To

Note: No specimen should be rejected. If specimen not received at appropriate temperature or in wrong anticoagulant, include note to laboratory. If questions, contact laboratory.

Clinical Information

Individuals with autism spectrum disorders, individuals with supernumerary chromosomes suspicious for a chromosome 15 origin, individuals with duplications of 15q11-q13 detected by multiplex ligation-dependent probe amplification (MLPA) or other testing methodologies (to distinguish between interstitial tandem duplication and supernumerary marker).

 

Cytogenetic abnormalities at the 15q11-q13 locus are reported in up to 4% of patients with autism spectrum disorders. Duplications in this chromosome region can occur as an interstitial tandem repeat or as a supernumerary isodicentric chromosome 15, leading to trisomy or tetrasomy of genes at the 15q11-q13 locus. The majority of interstitial tandem repeats in this region are not detectable by conventional chromosome analysis but can be identified by FISH. Supernumerary chromosomes can often be identified by conventional chromosome analysis but their origin must be confirmed by FISH analysis. Molecular analysis by MLPA can also detect duplications of chromosome 15q, but FISH analysis is necessary to distinguish between interstitial tandem duplication and a supernumerary marker.

 

The phenotype associated with these abnormalities depends largely on the amount of duplicated material, as well as parent of origin. Small dicentric markers with little 15q material duplicated are often familial and result in a normal phenotype. Larger dicentric 15 markers are usually new mutations and result in mild dysmorphic features, mental retardation, and behavioral abnormalities consistent with autism. Interstitial tandem duplications are associated with autistic spectrum disorders when maternally inherited, but paternally inherited duplications are less likely to cause phenotypic effects.

Interpretation

Specimens with a normal signal pattern in metaphase and interphase cells are considered negative for this probe.

 

Specimens with a FISH signal pattern indicating duplication of the critical region (3 signals) will be reported as having a duplication of the region tested by this probe.

Cautions

Because this FISH test is not approved by the US Food and Drug Administration, it is important to correlate 15q11.2 duplications by other established methods, such as clinical history or physical evaluation.

 

This test is not designed to identify 15q deletions or diagnose Prader-Willi/Angelman syndromes

 

Interfering factors:

-Cell lysis caused by forcing the blood quickly through the needle

-Use of an improper anticoagulant or improperly mixing the blood with the anticoagulant

-Excessive transport time

-Inadequate amount of specimen may not permit adequate analysis

-Improper packaging may result in broken, leaky, and contaminated specimen during transport

-Exposure of the specimen to temperature extremes (freezing or >30° C) may kill cells and interfere with attempts to culture cells

-In prenatal specimens, a bloody specimen may interfere with attempts to culture cells and contamination by maternal cells may cause interpretive problems

Clinical Reference

1. Mao R, Jalal SM, Snow K, et al: Characteristics of two cases with dup(15)(q11.2-q12): one of maternal and one of paternal origin. Genet Med 2000;2:131-135

2. Thomas JA, Johnson J, Peterson Kraai TL, et al: Genetic and clinical characterization of patients with an interstitial duplication 15q11-q13, emphasizing behavioral phenotype and response to treatment. Am J Med Genet 2003;119:111-120

3. Battaglia A: The inv dup(15) or idic(15) syndrome: a clinically recognizable neurogenetic disorder. Brain Dev 2005;5:365-369

4. Muhle R, Trentacoste S, Rapin I: The genetics of autism. Pediatrics 2004;113:472-486

5. Dennis NR, Veltman MW, Thompson R, et al: Clinical findings in 33 subjects with large supernumerary marker(15) chromosomes and 3 subjects with triplication of 15q11-q13. Am J Med Genet A 2006;140:434-441

Method Description

This FISH test involves 2 commercially available DNA probes (D15S10 and SNRPN) and analysis is performed on metaphase cells and interphase nuclei. Analysis of metaphase cells is performed to determine whether the 15q duplication is the result of an interstitial duplication or a supernumerary dicentric marker. Since tandem 15q duplications of SNRPN may be difficult to detect on metaphase cells, interphase nuclei are scored to identify duplications, which are represented by the observation of 3 target probe signals.(Unpublished Mayo method)

Day(s) and Time(s) Performed

Samples processed Monday through Sunday. Results reported Monday through Friday, 8 a.m.-5 p.m.

Analytic Time

12 days

Specimen Retention Time

Amniotic Fl. (remaining supernatant/whole fluid aliquots): Discarded 14 days after report. Blood: 4 weeks. Products of Conception (identifiable fetal tissue): Cremated quarterly after results reported. All Other Specimens: Discarded when results reported.

Performing Laboratory

Mayo Medical Laboratories in Rochester

CPT Code Information

88271x2, 88291 – DNA probe, each (first probe set), Interpretation and report

88271x2 – DNA probe, each; each additional probe set (if appropriate)

88271x1 – DNA probe, each; coverage for sets containing 3 probes (if appropriate)

88271x2 – DNA probe, each; coverage for sets containing 4 probes (if appropriate)

88271x3 – DNA probe, each; coverage for sets containing 5 probes (if appropriate)

88273 w/modifier 52-Chromosomal in situ hybridization, less than 10 cells (if appropriate)

88273-Chromosomal in situ hybridization, 10-30 cells (if appropriate)

88274 w/modifier 52 – Interphase in situ hybridization, <25 cells, each probe set (if appropriate)

88274 – Interphase in situ hybridization, 25 to 99 cells, each probe set (if appropriate)     

88275 – Interphase in situ hybridization, 100 to 300 cells, each probe set (if appropriate)

 

LOINC Code Information

Test ID Test Order Name Order LOINC Value
D15F 15q11.2 Duplication, FISH In Process

 

Result ID Test Result Name Result LOINC Value
51857 Result Summary 50397-9
51859 Interpretation 69965-2
54539 Result In Process
CG671 Reason For Referral 42349-1
CG672 Specimen 31208-2
51860 Source 31208-2
51861 Method 49549-9
51858 Additional Information 48767-8
53874 Disclaimer 62364-5
51862 Released By 18771-6

Test Classification

This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

Forms

New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.